Transdermal delivery of certain drugs has been possible for many years. Transdermal drug delivery devices are generally laminated composites that include a pressure-sensitive adhesive layer which may contains the drug and by which the device is attached to the skin and a backing layer which forms the outer surface of the device, which may form a reservoir for the drug, and which is impermeable to the drug. To date, commercial exploitation of transdermal drug delivery systems has been limited to only a few specific active agents, because of the practical problems to be overcome. These problems include the solubility of the drug, the effect of the drug on the adhesive layer and delivery of the drug to the skin and through the stratum corneum and viable epidermis into the systemic circulation at a constant rate over a prolonged period. In addition, transdermal drug delivery devices must maintain their integrity during storage prior to use.
Transdermal delivery is difficult because of skin's highly impermeable outer layer called stratum corneum. The stratum corneum is 10-20 μm thick and, unlike other tissues in the body, contains “cells” filled with bundles of cross-linked keratin and keratohyalin surrounded by an extracellular matrix of lipids assembled in multiple bilayer structures. There are no blood vessels or nerves in stratum corneum. Below stratum corneum is the viable epidermis, which is 50-100 μm thick and also contains no blood vessels, but has some nerves. Deeper still is the dermis, which measures 1-2 mm thick and contains blood vessels, lymphatics and nerves. Drugs that cross the stratum corneum barrier can generally diffuse to the capillaries in the superficial dermis for absorption and systemic distribution. For this reason, most approaches to increase transdermal delivery have emphasized disruption of stratum corneum microstructure using chemical or physical methods.
Conventional drug delivery using pills or injection is often not suitable for most protein or biotech active agents, DNA and other nucleic acid constructs, and other therapies currently proposed and envisioned. An attractive alternative would be transdermal delivery from a patch, which avoids degradation in the gastrointestinal tract and first-pass effects of the liver associated with oral delivery as well as the pain and inconvenience of intravenous injection. Transdermal drug delivery also offers the possibility to continuously control the delivery rate, in contrast to conventional methods that deliver a large, discrete bolus. These advantages have led to a multi-billion dollar market for transdermal patches used for smoking cessation (nicotine), hormone replacement (estradiol), and other indications. Despite these advantages, transdermal drug delivery is severely limited by the poor permeability of human skin; most drugs do not cross skin at therapeutic rates and only a dozen drugs have been approved by FDA for transdermal delivery since the first patch was introduced 25 years ago. The skin's barrier properties are due to the highly impermeable outer layer called stratum corneum, which is 10-20 μm thick. Drugs that cross the stratum corneum barrier can generally diffuse to deeper capillaries for systemic distribution. For this reason, most approaches to increase transdermal delivery have emphasized disruption of stratum corneum microstructure using chemical or physical methods. Currently approaches exist to physically disrupt the stratum corneum using heating filaments or an array of electrodes to generate Joule heating by passing a short, high-current electric pulse. These devices are all powered by means of wires physically connected to an external DC or RF power supply.
What is needed are methods and devices that can increase the permeability of barriers, such as skin, that do not require the physical connection of wires to link the power supply to the components that are causing the increase in permeability. Further, what is needed are methods and devices that provide for transdermal transfer of a greater variety of active agents. Additionally, what is also needed are methods and devices that can aid in detecting and measuring analytes that are contained within a barrier, particularly skin or other membranes.